The overall objective of this research is to develop general synthetic methodology which will allow the synthesis of variously substituted multi-hydroxamic acid containing compounds capable of binding and transporting iron. Natural hydroxaimic acids and the corresponding ferric chelates have been implicated in a wide spectrum of biological activities. Cyclic trihydroxamic acids have successfully treated iron storage diseases in children and are now under consideration for treatment of related diseases such as Cooley's anemia. Study of such compounds might also facilitate the understanding of essential biological iron transport mechanisms. Specific synthetic targets now being pursued in order to demonstrate the proposed methodology are trihydroxamate containing ferrichromes and related peptide analogs, the bis-hydroxamate diketopiperazine rhodotorulic acid (a compound of considerable interest which is now entering clinical trials for treatment of iron storage diseases), mycobactin (a growth factor for mycobacterium paratuberculosis (M. johnei), the organism responsible for Johne's disease in cattle), aerobactin, and the unusual constituent amino acids delta-N-hydroxy-L-ornithine and N-hydroxyl-L-lysine. The key to the synthesis of these important multihydroxamic acid containing compounds is the development of a method of introduction of the hydroxamate functionality under conditions compatible with the other molecular components to be incorporated. We have recently developed a very efficient process for the direct N-alkylation of substituted hydroxamic acids with alcohols under extremely mild conditions. The process avoids several steps previously needed to accomplish the synthesis of complex hydroxamic acids. these results, once fully incorporated into the synthesis of appropriate molecules previously mentioned, should significantly aid studies necessary to elucidate structure-activity relationships in these biologically important molecules.